PodcastViewing Islet Cell Function

Transcript


Narrator:
The Diabetes Research Institute presents a series of reports on the latest progress in cure focused research. Promising discoveries aimed at restoring natural insulin production in those living with diabetes.  

Reporter:
Recent studies show that patients with type 1 diabetes can achieve insulin independence and normalized blood sugar control when they receive infusions of healthy, human insulin-producing cells.
 
The cells that produce insulin are called beta cells. They live inside clusters of cells called islets

But, over time, these transplanted islet cells lose function and most patients return to using low doses of insulin.  

The loss of function is a result of many factors, and scientists are addressing them.

But until now, the research has been conducted, in large part, in the lab -- using indirect monitoring tools which do not reflect the natural, live environment.  

Now, for the first time, scientists are actually able to see how the transplanted islets function when they are inside of a living organism.  

In a collaboration between the DRI and the Karolinska Institute in Stockholm, Sweden, researchers transplanted islets in the eye of a mouse, and then viewed the transplant through the mouse’s cornea, as if it were a living window.  

The study is published in Nature Medicine. One of the senior authors is Per-Olof Berggren, Ph.D.  

We spoke with Dr. Berggren by phone from Stockholm, Sweden.

Berggren:
We wanted to try to create the model where we could study the beta cell function and survival under conditions which were more close to what we have in the living organism. So then we were thinking of using the eye as a natural body window to actually be able to look into the insulin-secreting cells from outside.

If one look at all of these complex mechanisms that are regulating the function and survival of the insulin-secreting cells, one can basically label all of this specific mechanisms with markers. The markers are sending out light, we are calling it, that they are "fluorescently labeled." We can transplant these islets with these markers into the eye and then we can follow the insulin-secreting cells by studying the markers through a sophisticated microscope.

We can study phenomenon at the cell, single cell level, so we can in detail see the function of this one single cell and we can stand back from the outside, look in, viewing how this cell is behaving under different conditions.

We have a fantastic window to study cell function in the living organism for the first time ever.

Reporter:
So now you have the ability to watch these islets function. What have you seen so far?

Berggren:
The islets that we are transplanting into the eye are getting vascularized very rapidly, so we get a very nice capillary network within a month that very efficiently can support the insulin-secreting cells with blood. Secondly, we have been able to show that important signals that are regulating insulin release can be measured very effectively in the pancreatic beta cell in the eye.

Reporter:
How will this help us understand why islets lose function over time? How will this help us make the islets potentially live longer?

Berggren:
If we are going to understand how beta cells are functioning, why they are surviving, why they are not surviving, then we need to take into account all of the influence that's surrounding cells: blood vessels, components, nerves and so on, and this is something that we can never do in the test tube in the laboratory. But, by looking through the eye, we have the possibility to do this. This is the only way one can study this at the moment.

The second thing is, of course, that if we now start to transplant into animals of different strains and start to look at immunological reactions, then of course, we can also use and test novel immunosuppressive drugs and see how they are interfering with the immune response. So that means that we should be able to identify very nicely, in a very clean system, the potential of novel, less harmful, less tough immunosuppressive drugs for the patient. 

Reporter:
So do you see this then being repeated then in other kinds of species, not just in the mouse?

Berggren:
Yes, we would of course like very much to do this in non-human primates to begin with, to see how the islets, if they are transplanted into these bigger animals, behave.

Reporter: 
People that'll be listening to this who have diabetes, who have loved ones with diabetes -- why should they be excited about this? How does this move us ultimately closer to a cure?  

Berggren:
It moves us closer to a cure from one very important standpoint. All of the studies that people have been doing all over the world for many, many years now have been limited to the ability to study  isolated pancreatic islets or cells, taking out from animals or human beings, and that is too much of a simplification.

So the only way to understand what is going wrong is to study it in in vivo, in a live organism situation. So that is what this platform will bring to us. It's an extremely versatile tool to study pancreatic beta cell development, function, proliferation, cell death, gene expression, also complications because we can study  in this model how vessels, how nerves normally are associating themselves with insulin-secreting cells.

But also, if you are looking into type 2 diabetes, of course, there is an enormous need for screening of novel compounds that can be used in the treatment of the disease and here we have a fantastic in vivo screening tool. In other words, we can screen drugs in living organisms which you cannot do today.

Narrator:
This has been a production of the Diabetes Research Institute Foundation. For more information or to show your support for the Diabetes Research Institute, call 1-800-321-3437.

You may also donate online at DiabetesResearch.org.


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